anandamide and Weight-Loss

Development of the metabolic syndrome results from the interaction of genetic and environmental factors. Metabolic syndrome together with smoking represents risk factors for the development of cardiovascular complications. They may result from the hyperstimulation of the endocannabinoid system. The CB1 receptor has been assumed to play an important role in the endocannabionoid system. It is abundantly expressed in the brain, and in other parts of human body such as in the fat tissue. Rimonabant is a selective blocker of cannabinoid-1 (CB1) receptors and participates in the regulation of impaired endocannabinoid system. In the overweight humans, it stimulates sustained reduction of the body weight, girth size and it improves lipid and glucose metabolism. Rimonabant also reduces nicotine self-administration and may be effective not only as an aid for smoking cessation but also in the prevention of body weight increase related to the smoking cessation as it was documented in Rio-Lipids and Stratus-us studies.

Topics: Arachidonic Acids; Cannabinoid Receptor Antagonists; Cannabinoid Receptor Modulators; Endocannabinoids; Humans; Metabolic Syndrome; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Rimonabant; Smoking; Smoking Cessation; Weight Loss

Despite the importance of dairy proteins in modifying of metabolic abnormalities, no attention has been given to their effects on endocannabinoids.. A total number of 60 obese women were recruited in a 2-month randomized clinical trial. Following random allocation, they were assigned to one of the two groups: control (n = 30) and intervention (n = 30). Then, all the subjects followed a hypocaloric diet of 800 kcal below estimated energy needs. The intervention group received isocaloric weight-loss diet and whey protein powders (30 g/day). Baseline and 2-month fasting anthropometric, blood glucose, serum insulin, insulin resistance, lipid profile, AEA, and 2-AG were measured.. The study groups were homogenous in terms of baseline characteristics (p > 0.05) except for MUFA intake (p = 0.021). There were no significant differences in energy and macronutrient intakes in the intervention group compared to the control group at the end of the study (p > 0.05). The results of the ANCOVA did not show significant reductions in body weight and BMI of the intervention group compared to the control group (p > 0.05); however, WC, body fat, FBS, AEA, 2-AG, total cholesterol, and triglyceride decreased and HDL-c significantly increased in the intervention group compared to the control group (p < 0.05).. In this study, the effects of simultaneous weight-loss diet and whey protein supplementation on the reduction of endocannabinoids were determined.. Iranian Registry of Clinical Trials IRCT2017021410181N8 . Registered on March 2017.

Topics: Adult; Arachidonic Acids; Blood Glucose; Body Mass Index; Diet, Reducing; Dietary Supplements; Endocannabinoids; Fasting; Female; Humans; Insulin; Iran; Lipids; Obesity; Polyunsaturated Alkamides; Premenopause; Weight Loss; Whey Proteins

Topics: Adolescent; Adult; Affect; Aged; Anger; Anxiety; Arachidonic Acids; Cardiorespiratory Fitness; Endocannabinoids; Exercise; Female; Humans; Male; Middle Aged; Physical Fitness; Polyunsaturated Alkamides; Quality of Life; Weight Loss; Young Adult

The endocannabinoid system (ECS) promotes weight gain and obesity-associated metabolic changes. Weight loss interventions may influence obesity-associated risk indirectly through modulation of the peripheral ECS. We investigated the effect of acute and chronic treatment with sibutramine on components of the peripheral ECS.. Twenty obese otherwise healthy patients received randomized, double-blind, crossover treatment with placebo and 15 mg/day sibutramine for 5 days each, followed by 12 weeks open-label sibutramine treatment. We determined circulating anandamide and 2-arachidonoylglycerol and expression levels of endocannabinoid genes in subcutaneous abdominal adipose tissue biopsies.. Body weight was stable during the acute treatment period and decreased by 6.0+/-0.8 kg in those patients completing 3 months of sibutramine treatment (P<0.05). Circulating endocannabinoids and the expression of ECS genes did not change with acute or chronic sibutramine treatment.. The ECS is activated in obesity. We did not find any influence of 5% body weight loss induced by sibutramine on circulating levels of endocannabinoids and adipose-tissue expression of endocannabinoid genes in obese subjects. These data confirm our previous findings on dietary weight loss and suggest that the dysregulation of the ECS may be a cause rather than a consequence of obesity.

Topics: Abdominal Fat; Adolescent; Adult; Appetite Depressants; Arachidonic Acids; Biopsy; Body Weight; Cannabinoid Receptor Modulators; Cross-Over Studies; Cyclobutanes; Dose-Response Relationship, Drug; Double-Blind Method; Endocannabinoids; Gene Expression Regulation; Glycerides; Humans; Middle Aged; Obesity; Polyunsaturated Alkamides; Regression Analysis; Weight Loss

Topics: Adult; Aged; Amides; Arachidonic Acids; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Cholesterol; Diet, High-Protein; Endocannabinoids; Ethanolamines; Glycerides; Humans; Lipoproteins, LDL; Middle Aged; Oleic Acids; Palmitic Acids; Polyunsaturated Alkamides; Weight Loss

Endocannabinoids (ECs) are associated with obesity and ectopic fat accumulation, both of which play a role in the development of cardiovascular disease (CVD) in type 2 diabetes (T2D). The effect of prolonged caloric restriction on ECs in relation to fat distribution and cardiac function is still unknown. Therefore, our aim was to investigate this relationship in obese T2D patients with coronary artery disease (CAD).. In a prospective intervention study, obese T2D patients with CAD (n = 27) followed a 16 week very low calorie diet (VLCD; 450-1000 kcal/day). Cardiac function and fat accumulation were assessed with MRI and spectroscopy. Plasma levels of lipid species, including ECs, were measured using liquid chromatography-mass spectrometry.. Caloric restriction in T2D patients with CAD decreases AEA levels, but not 2-AG levels, which is paralleled by decreased lipid accumulation in adipose tissue, liver and heart, and improved cardiovascular function. Interestingly, baseline AEA levels strongly correlated with SAT volume. We anticipate that dietary interventions are worthwhile strategies in advanced T2D, and that reduction in AEA may contribute to the improved cardiometabolic phenotype induced by weight loss.

Topics: Adipose Tissue; Aged; Arachidonic Acids; Body Fat Distribution; Caloric Restriction; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diet, Reducing; Endocannabinoids; Energy Intake; Ethanolamines; Female; Glycerides; Heart; Humans; Lipid Metabolism; Liver; Male; Middle Aged; Myocardium; Obesity; Polyunsaturated Alkamides; Prospective Studies; Ventricular Function, Left; Weight Loss

The individual weight loss response to obesity treatment is diverse. Here we test the hypothesis that the weight loss response to the CB1 receptor antagonist rimonabant is influenced by endogenous levels of receptor agonists. We show that baseline anandamide levels and body weight independently contribute to predict the treatment response to rimonabant in rodents, demonstrating that addition of biomarkers related to mode of action is relevant for a personalized health care approach to obesity treatment.

Topics: Animals; Arachidonic Acids; Body Weight; Cannabinoid Receptor Antagonists; Endocannabinoids; Male; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Rimonabant; Weight Loss

To measure the circulating levels of endocannabinoids and related molecules at fasting, after acute hyperinsulinemia and after weight loss in insulin sensitive vs. insulin resistant obese postmenopausal women.. The sample consisted of 30 obese postmenopausal women (age: 58.9 ± 5.2 yrs; BMI: 32.9 ± 3.6 kg/m(2) ). Subjects underwent a 3-hour hyperinsulinaemic-euglycaemic clamp (HEC) (glucose disposal rate (M-value): 10.7 ± 3.3 mg min(-1) kg(-1) FFM) and 6-month weight loss intervention. Participants were classified as insulin sensitive obese (ISO) or insulin resistant obese (IRO) based on a predefined cutoff. Plasma levels of the endocannabinoids, anandamide (AEA), 2-arachidonoylglycerol (2-AG), and of the AEA-related compounds, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), were measured by liquid chromatography-mass spectrometry.. IRO presented higher levels of 2-AG (P < 0.05) independently of the HEC and weight loss, whereas the HEC had an independent inhibitory effect on AEA, PEA, and OEA levels (P < 0.05) in both groups. Furthermore, there was an independent stimulatory effect of weight loss only on PEA levels in both groups (P < 0.05).. This study is the first to show that higher circulating levels of the endocannabinoid 2-AG are found in IRO compared to ISO postmenopausal women, and that weight loss is associated with an increase in PEA, a PPAR-α ligand.

Topics: Amides; Arachidonic Acids; Body Composition; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Cohort Studies; Endocannabinoids; Ethanolamines; Female; Glucose Clamp Technique; Glycerides; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Middle Aged; Obesity; Oleic Acids; Palmitic Acids; Polyunsaturated Alkamides; Postmenopause; Triglycerides; Weight Loss

Obesity is the main risk factor for the development of type 2 diabetes. Activation of the central endocannabinoid system increases food intake and promotes weight gain. Blockade of the cannabinoid type 1 (CB-1) receptor reduces body weight in animals by central and peripheral actions; the role of the peripheral endocannabinoid system in human obesity is now being extensively investigated. We measured circulating endocannabinoid concentrations and studied the expression of CB-1 and the main degrading enzyme, fatty acid amide hydrolase (FAAH), in adipose tissue of lean (n = 20) and obese (n = 20) women and after a 5% weight loss in a second group of women (n = 17). Circulating levels of anandamide and 1/2-arachidonoylglycerol were increased by 35 and 52% in obese compared with lean women (P < 0.05). Adipose tissue mRNA levels were reduced by -34% for CB-1 and -59% for FAAH in obese subjects (P < 0.05). A strong negative correlation was found between FAAH expression in adipose tissue and circulating endocannabinoids. Circulating endocannabinoids and CB-1 or FAAH expression were not affected by 5% weight loss. The expression of CB-1 and FAAH was increased in mature human adipocytes compared with in preadipocytes and was found in several human tissues. Our findings support the presence of a peripheral endocannabinoid system that is upregulated in human obesity.

Topics: Adipose Tissue; Amidohydrolases; Arachidonic Acids; Body Composition; Body Mass Index; Cannabinoid Receptor Modulators; Endocannabinoids; Female; Gene Expression; Glycerides; Humans; Linear Models; Middle Aged; Obesity; Polyunsaturated Alkamides; Postmenopause; Receptor, Cannabinoid, CB1; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Weight Loss